SARS-CoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity

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The need for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) next-generation vaccines has been highlighted by the rise of variants of concern (VoCs) and the long-term threat of emerging coronaviruses. Here, we design and characterize four categories of engineered nanoparticle immunogens...

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Detalles Bibliográficos
Autores principales: Joyce, M. Gordon, Chen, Wei-Hung, Sankhala, Rajeshwer S., Hajduczki, Agnes, Thomas, Paul V., Choe, Misook, Martinez, Elizabeth J., Chang, William C., Peterson, Caroline E., Morrison, Elaine B., Smith, Clayton, Chen, Rita E., Ahmed, Aslaa, Wieczorek, Lindsay, Anderson, Alexander, Case, James Brett, Li, Yifan, Oertel, Therese, Rosado, Lorean, Ganesh, Akshaya, Whalen, Connor, Carmen, Joshua M., Mendez-Rivera, Letzibeth, Karch, Christopher P., Gohain, Neelakshi, Villar, Zuzana, McCurdy, David, Beck, Zoltan, Kim, Jiae, Shrivastava, Shikha, Jobe, Ousman, Dussupt, Vincent, Molnar, Sebastian, Tran, Ursula, Kannadka, Chandrika B., Soman, Sandrine, Kuklis, Caitlin, Zemil, Michelle, Khanh, Htet, Wu, Weimin, Cole, Matthew A., Duso, Debra K., Kummer, Larry W., Lang, Tricia J., Muncil, Shania E., Currier, Jeffrey R., Krebs, Shelly J., Polonis, Victoria R., Rajan, Saravanan, McTamney, Patrick M., Esser, Mark T., Reiley, William W., Rolland, Morgane, de Val, Natalia, Diamond, Michael S., Gromowski, Gregory D., Matyas, Gary R., Rao, Mangala, Michael, Nelson L., Modjarrad, Kayvon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651551/
https://www.ncbi.nlm.nih.gov/pubmed/34919799
http://dx.doi.org/10.1016/j.celrep.2021.110143
Descripción
Sumario:The need for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) next-generation vaccines has been highlighted by the rise of variants of concern (VoCs) and the long-term threat of emerging coronaviruses. Here, we design and characterize four categories of engineered nanoparticle immunogens that recapitulate the structural and antigenic properties of the prefusion SARS-CoV-2 spike (S), S1, and receptor-binding domain (RBD). These immunogens induce robust S binding, ACE2 inhibition, and authentic and pseudovirus neutralizing antibodies against SARS-CoV-2. A spike-ferritin nanoparticle (SpFN) vaccine elicits neutralizing titers (ID(50) > 10,000) following a single immunization, whereas RBD-ferritin nanoparticle (RFN) immunogens elicit similar responses after two immunizations and also show durable and potent neutralization against circulating VoCs. Passive transfer of immunoglobulin G (IgG) purified from SpFN- or RFN-immunized mice protects K18-hACE2 transgenic mice from a lethal SARS-CoV-2 challenge. Furthermore, S-domain nanoparticle immunization elicits ACE2-blocking activity and ID(50) neutralizing antibody titers >2,000 against SARS-CoV-1, highlighting the broad response elicited by these immunogens.

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